This profile describes a study conducted in primary care centres in Malawi, investigating accuracy and broader clinical, and antimicrobial resistance impact of using trial-of-antibiotics to “rule out” tuberculosis among adults presenting with cough. Dr Titus Divala and his team share the context and resources produced for a systematic review and three arm (625 per arm) individually randomised (1:1:1), open-label controlled clinical trial which investigated whether treatment with broad-spectrum antibiotics continue being used as a diagnostic tool for Tuberculosis.
With 1.4 million deaths in 2019, tuberculosis remains a leading global infectious cause of death, second only to COVID-19 in 2020. Antimicrobial resistant infections are projected to cause over 10 million deaths annually by 2050, in part reflecting non-pathogen directed prescription secondary to limited point-of-care diagnostics and laboratory infrastructure. These two major global public health and economic threats intersect through diagnostic algorithms that have for decades encouraged broad-spectrum antibiotic prescriptions (“trial-of-antibiotics”) during the diagnostic work-up leading to ~5 million people being treated annually for mycobacteriology-negative tuberculosis.
Current point-of-care laboratory tests for detecting tuberculosis (TB) are suboptimal, they fail to detect TB in as many as 50% of tested individuals. Considering that TB is a life-threatening illness, there was need to still detect as many infected people as possible. To achieve this, standard TB diagnostic guidelines include giving patients antibiotic treatment that can treat most causes of respiratory symptoms except TB. Therefore, if a patient improves after the treatment, the possibility of TB is very narrow but if they don’t improve, they are deemed more likely to have TB. In other words, we use antibiotic treatment as a diagnostic test for TB where current standard tests are likely to have missed the disease.
The underlying assumption that post-treatment symptom improvement “rules out” tuberculosis, had no clear evidence-base despite being in use for decades. The ACT-TB Study investigated the prevailing evidence gaps through a systematic review and RCT.
Want to know more about this study? Watch Dr Titus Divala's presentation as part of the AMR Knowledge Hub launch webinar: Global Health Research Priorities for Responding to the AMR Silent Pandemic, where he shared findings from this trial. You can read a transcript of this presentation in the webinar report.
The trial was completed, and results are currently undergoing peer review ahead of publication.
The work was sponsored by the London School of Hygiene & Tropical Medicine (LSHTM) and implemented under the Kamuzu University of Health Sciences (formerly University of Malawi College of Medicine). The work was also affiliated with the LSHTM TB Centre, the LSTHM AMR Centre, and the Malawi Liverpool Wellcome Trust.
Funding was provided by the Helse Nord RHF (Titus Divala), Commonwealth Scholarship Commission (Titus Divala), Wellcome Trust Senior Research Fellowship in Clinical Science (WT200901, Liz Corbett), and the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) (MR/K012126/1, Katherine Fielding).
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